ArticleInfection and immunity2011
Two DHH subfamily 1 proteins contribute to pneumococcal virulence and confer protection against pneumococcal disease.
Article in Infection and immunity, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 33 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
33 citing papers in PubMed, 45 citations in OpenAlex.
- Cyclic Di-AMP Affects Cell Membrane Integrity of Streptococcus pneumoniae.Molecular microbiology · 2025Article
- Structural and functional investigation of the DHH/DHHA1 family proteins in Deinococcus radiodurans.Nucleic acids research · 2024Article
- Loss of Pde1 function acts as an evolutionary gateway to penicillin resistance inProceedings of the National Academy of Sciences of the United States of America · 2023Article
- An atypical GdpP enzyme linking cyclic nucleotide metabolism to osmotic tolerance and gene regulation inFrontiers in microbiology · 2023Article
- Interspecies recombination, not de novo mutation, maintains virulence after β-lactam resistance acquisition in Streptococcus pneumoniae.Cell reports · 2022Article
- Cyclic-di-AMP Phosphodiesterase Elicits Protective Immune Responses AgainstFrontiers in cellular and infection microbiology · 2022Article
- Regulation and distinct physiological roles of manganese in bacteria.FEMS microbiology reviews · 2021Review
- Beyond Homeostasis: Potassium and Pathogenesis during Bacterial Infections.Infection and immunity · 2021Review
- Identification of conditionally essential genes forVirulence · 2020Article
- Increased Excess Intracellular Cyclic di-AMP Levels Impair Growth and Virulence of Bacillus anthracis.Journal of bacteriology · 2020Article
- Cyclic di-AMP, a second messenger of primary importance: tertiary structures and binding mechanisms.Nucleic acids research · 2020Review
- Bacterial Second Messenger Cyclic di-AMP Modulates the Competence State in Streptococcus pneumoniae.Journal of bacteriology · 2020Article
- Unique Roles forFrontiers in immunology · 2020Article
- Effect of FHA and Prn on Bordetella pertussis colonization of mice is dependent on vaccine type and anatomical site.PloS one · 2020Article
- The Second Messenger c-di-AMP Regulates Diverse Cellular Pathways Involved in Stress Response, Biofilm Formation, Cell Wall Homeostasis, SpeB Expression, and Virulence in Streptococcus pyogenes.Infection and immunity · 2019Article
- Stress Suppressor Screening Leads to Detection of Regulation of Cyclic di-AMP Homeostasis by a Trk Family Effector Protein in Streptococcus pneumoniae.Journal of bacteriology · 2018Article
- Coping with an Essential Poison: a Genetic Suppressor Analysis Corroborates a Key Function of c-di-AMP in Controlling Potassium Ion Homeostasis in Gram-Positive Bacteria.Journal of bacteriology · 2018Article
- Review
- Panel 6: Vaccines.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2017Review
- Panel 4: Report of the Microbiology Panel.Otolaryngology--head and neck surgery : official journal of American Academy of Otolaryngology-Head and Neck Surgery · 2017Review
Corrections and comments
- Erratum issued
Authors and funding
7 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Streptococcus pneumoniae is an important human bacterial pathogen, causing such infections as pneumonia, meningitis, septicemia, and otitis media. Current capsular polysaccharide-based conjugate vaccines protect against a fraction of the over 90 serotypes known, whereas vaccines based on conserved pneumococcal proteins are considered promising broad-range alternatives. The pneumococcal genome encodes two conserved proteins of an as yet unknown function, SP1298 and SP2205, classified as DHH (Asp-His-His) subfamily 1 proteins. Here we examined their contribution to pneumococcal pathogenesis using single and double knockout mutants in three different strains: D39, TIGR4, and BHN100. Mutants lacking both SP1298 and SP2205 were severely impaired in adherence to human epithelial Detroit 562 cells. Importantly, the attenuated phenotypes were restored upon genetic complementation of the deleted genes. Single and mixed mouse models of colonization, otitis media, pneumonia, and bacteremia showed that bacterial loads in the nasopharynx, middle ears, lungs, and blood of mice infected with the mutants were significantly reduced from those of wild-type-infected mice, with an apparent additive effect upon deletion of both genes. Minor strain-specific phenotypes were observed, i.e., deletion of SP1298 affected host-cell adherence in BHN100 only, and deletion of SP2205 significantly attenuated virulence in lungs and blood in D39 and BHN100 but not TIGR4. Finally, subcutaneous vaccination with a combination of both DHH subfamily 1 proteins conferred protection to nasopharynx, lungs, and blood of mice infected with TIGR4. We conclude that SP1298 and SP2205 play a significant role at several stages of pneumococcal infection, and importantly, these proteins are potential candidates for a multicomponent protein vaccine.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.